tbuckley/cabot-search huggingface dataset:
Gender disparities in metastatic RCC therapies and outcomes.
Authors: Olivia French Gordon, Romtin Nadjafi, Vincent Xu, Arthur Drouaud, Michael Joseph Whalen, Yifeng Wang
Journal: Journal of Clinical Oncology (2023)

4565 Background: The incidence of metastatic renal cell carcinoma (mRCC) is rising globally in both males and females. Previous studies have shown that females with mRCC experience better overall survival (OS) when compared to males. In the era of immunotherapy (IM) as part of standard of care, gender-based outcome disparities are unclear. In this study, we identify gender-specific trends in treatment regimen and OS. Methods: The National Cancer Database (NCDB) was queried from 2004 to 2019 for a retrospective cohort analysis of mRCC patients. 51,596 males and 25,528 females were reviewed. The primary endpoints were OS and predictors of receipt of IM. Kaplan-Meier (KM) analysis was used to assess gender-based OS and compare OS in patients who received or did not receive CN or IM. Binomial logistic regression was performed to examine gender as a predictor of treatment received. Cox proportional hazards model assessed the impact of age, gender, sites of metastases, Charleson-Deyo comorbidity classification, insurance type, treatment facility, year of diagnosis, CN, and IM on OS. Results: In KM analyses, females had lower median OS compared to males (7.200 months vs 8.940 months, p&lt;0.001). Higher median OS was found in patients who received IM (21.3 vs 7.6 months; p&lt;0.001) and CN (22.1 vs 5.13 months; p&lt;0.001). Logistic regression demonstrated that females were less likely to receive IM after controlling for the variables listed above (OR 0.839 (95% CI: 0.787 - 0.894), p&lt;0.001). Cox regression demonstrated that when adjusting for clinicopathologic variables and treatment regimen, female gender independently conferred a statistically significant negative impact on OS (HR = 1.039 (95% CI: 1.015-1.063), p=0.001). Conclusions: While CN remains an efficacious treatment option, advances in IM have led to targeted therapies that improve OS in mRCC patients. We demonstrate that a gender-based discrepancy in mRCC survival persists. In contrast to previous literature, our analysis found worse OS as well as an underutilization of IM in female mRCC patients. Moreover, females with mRCC have increased mortality even when accounting for IM. Therefore, further investigation is needed to elucidate the causes of survival discrepancy in the modern era of mRCC treatment. [Table: see text]
Safety and efficacy of HB0025, an anti-PD-1/VEGF bispecific antibody fusion protein, in patients with advanced solid tumors: Preliminary results from an FIH trial.
Authors: Yiqun Du, Jian Zhang, Meili Sun, Qing Wen, Yawen Zheng, Anthony W. Tolcher, David Sommerhalder, Zhen Wang, Xiumin Li, Zhenyuan Gao, Huan Zhou, Lian Liu, Benjie Wang, Xiangyang Zhu, Yongmin Yang, Yang Yang, Chao Li, Jiangfeng Li
Journal: Journal of Clinical Oncology (2023)

2589 Background: HB0025 is a recombinant humanized anti-PD-L1 monoclonal antibody-VEGFR1 fusion Protein. Nonclinical data both in vitro and vivo have shown high-affinity binding to both targets as well as the inhibition of tumor growth in animal models. Here, we present preliminary safety and efficacy data from a dose escalation phase I study of HB0025. Methods: Eligible patients(pts) were ≥18 years old (ECOG PS 0–1) who had advanced solid tumors (NSCLC, gynecological tumors, digestive system tumors, etc.) and failed standard treatment. This phase 1 dose escalation includes accelerated titration (0.01, 0.03, 0.1 and 0.3mg/kg) and conventional 3+3 dose escalation (1.0, 3.0, 6.0, 10, 12, 20, and 30.0 mg/kg). HB0025 is administered intravenously every 14 days (Q2W). Objectives include evaluation of safety, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and antitumor activity. Adverse events (AEs) were reported with CTCAE v5.0 and DLTs were evaluated within a 28-day window. Results: As of Aug 30th 2022, 30 pts including 8 male and 22 female from Caucasian and Mongoloid have received HB0025 at doses of 0.01 mg/kg (n=1), 0.03 mg/kg (n=2), 0.1 mg/kg (n=1), 0.3 mg/kg (n=1),1.0 mg/kg (n=3), 3.0 mg/kg (n=7), 6.0mg/kg (n=7), 10.0 mg/kg (n=5), and 12.0mg/kg (n=3) Q2W. Overall, the median age was 55 years and the median lines of previous treatment was four. Of the 22 evaluable pts dosed at ≥ 3 mg/kg Q2W, the ORR was 9.1% (2/22) and the disease control rate (DCR) was 50% [11/22]. Among the 2 responders, a CR (colorectal ca) pt whose prior therapy was no immune checkpoint inhibitor (ICI) or bevacizumab have continued more than 36 weeks; and a PR (NSCLC) pt with duration more than 18 weeks whose tumor was 60.2% regression and prior ICI failure. Till the date of submission, the therapy was continuing for the CR and PR pts. Treatment-related adverse events (TRAEs) occurred in 83.3% of pts. The grade 3 TRAEs occurred in 20% [6/30] and treatment-related SAEs occurred in 13.3% [4/30]. One DLT occurred in the 12.0mg/kg cohort. No death occurred related to HB0025. TRAEs leading to treatment discontinuation occurred in 13.3% of pts [4/30]. The most frequent TRAEs were hypertriglyceridemia (23.3%), hypercholesterolemia (23.3%), anemia (16.7%), alanine aminotransferase increase (16.7%), and proteinuria (13.3%). Conclusions: HB0025 shows manageable safety and promising anti-tumor activity in pts with various solid tumors. To better characterize the risk-benefit profile, HB0025 is currently enrolled at 20.0 mg/kg Q2W and is being explored at doses 10 mg/kg in expansion cohorts. The future data, including PK, PD and ADA will be presented. Clinical trial information: NCT04678908 .
Trends in hepatocellular carcinoma rates by age, region, race, and ethnicity: A SEER database population study 2000-2019.
Authors: Eve Schodowski, Akram Alkrekshi, Anas Al Zubaidi, Abdul Rahman Al Armashi
Journal: Journal of Clinical Oncology (2023)

e16179 Background: Liver cancer (LC) incidence has tripled over the past four decades, with hepatocellular carcinoma (HCC) being the most common type (72%). Further, LC mortality often coincides with incidence, as the disease is often fatal. To illustrate, the five-year survival rate (2012-2018) for LC is 21% at all stages, compared to lung cancer at 23% and colon cancer at 65%. While incidence and death rates of LC have stabilized in the past 5 years, troubling disparities have been identified when rates are stratified by region, age, race, and ethnicity. For example, HCC incidence in rural areas has increased by 5.7% annually, with rates approaching that of urban ones, despite a historically lower incidence. Consequently, as several inequalities in HCC have been established, the study herein aims to identify whether recognition of these disparities has helped to reduce their growth. Methods: We identified incidence rates of HCC from the Surveillance, Epidemiology and End Results Program database at 4-year time intervals from 2000-2019, stratified by age above (&gt;) and below (&lt;) 60, metropolitan (M) vs nonmetropolitan (NM) counties, race, and ethnicity. Next, we calculated percent change and percent difference in HCC rates across time intervals and groups to evaluate trends. Results: Percent change in rates of HCC has increased since 2000 in those &gt;60 in both M and NM areas with larger growth observed in NM counties. Conversely, between 2010 and 2019 HCC rates have declined in those &lt;60, with a steeper decline observed in M (-18.2%) vs NM (-10.0%) counties. Alarmingly, when 2015-2019 HCC rates are stratified by race/ethnicity, each minority group studied exhibited considerably higher rates of HCC when compared to whites and non-Latinos of the same age group and region (percent difference = &gt;60 M; &gt;60 NM; &lt;60 M; &lt;60 NM): Black (50.3%; 37.2%; 24.1%; 26.6%), American Indian (21.2%; 85.8%; 7.6%; 77.5%), Asian (17.3%; 17.8%; 21.1%; 28.1%), and Latino (39.0%; 45.6%; 40.0%; 36.1%). [Reference: white rates = 35.4; 31.7; 5.1; 4.9 and non-Latino rates = 36.5; 33; 2.4; 2.5, respectively, per 100,000 and age adjusted to the 2000 US Standard Population]. Conclusions: Recent data describes a stabilization in LC incidence and death rates over the past 5 years. However, when HCC incidence is stratified by age, region, race, and ethnicity, disconcerting trends continue to be revealed. As such, interventions should be targeted at those &gt;60, living in NM areas, and in the minority groups studied to combat these disparities. [Table: see text]
Phase I safety and preliminary efficacy of PM1003, a bispecific antibody targeting PD-L1 and 4-1BB, in patients with advanced solid tumors.
Authors: Junli Xue, Yuping Sun, DaPeng Li, Ye Guo
Journal: Journal of Clinical Oncology (2023)

e14511 Background: PM1003 is a VHH-based anti-PD-L1/4-1BB bispecific antibody. The anti-4-1BB VHH arm binds to a unique epitope at the CRD4 region of 4-1BB, activating 4-1BB signals through cross-linking in the presence of PD-L1 that is often upregulated in the tumor microenvironment, thus avoiding harm to healthy tissues. This is the First In Human study of PM1003. Methods: This study was conducted with a standard 3+3 dose escalation design (Part A: single doses of 0.02, 0.1, 1, 3, 6, and 10 mg/kg for DLT evaluation after 3 weeks followed by Q2W for further administration) and dose expansion (Part B). For Part A, the primary endpoint was safety and tolerability with secondary endpoint of ORR per RECIST 1.1. For Part B, ORR per RECIST 1.1 was the primary endpoint and the secondary endpoints were safety and PK. Results: As of February 9, 2023, a total of 17 subjects have received at least 1 dose of PM1003, including 16 subjects in Part A (3 subjects in each of the 0.02, 0.1, 1, 3 mg/kg dose levels respectively and 4 subjects in 6 mg/kg), and 1 subject in Part B (1 mg/kg Q2W). In Part A, no DLTs were observed up to 6 mg/kg. Of the 17 patients, TRAEs occurred in 15 subjects (88.2%), ≥ Grade 3 TRAEs occurred in 5 subjects (29.4%). No patient discontinued PM1003 administration due to TRAE. The most common TRAEs were anaemia (35.3%), neutrophil count decreased (29.4%), white blood cell count decreased (29.4%), platelet count decreased (29.4%), fatigue (23.5%). 11 subjects completed at least one efficacy evaluation in part A. The median duration of PM1003 exposure was 9.9 weeks (range, 3.1-31.1 weeks). The ORR per RECIST 1.1 was 9.1% with a DCR of 54.5%. Preliminary evidence of antitumor activity has been observed in 1 subject with gastric cancer (1 mg/kg Q2W) who was enrolled after previous surgery, chemotherapy, anti-PD-1 and anti-HER2-ADC treatment, and had a partial response of 87.8% in target lesion reduction during the first efficacy evaluation (7 weeks) after PM1003 treatment. T 1/2 of PM1003 of 1 mg/kg and 3 mg/kg dose level is 6.3 and 12.8 days, respectively. Receptor occupancy of PD-L1 in the 1 mg/kg and 3 mg/kg cohorts reached saturation at 336 hours after the first single dose and maintained at an almost stable state. Conclusions: PM1003 was well-tolerated up to 6 mg/kg and has shown preliminary anti-tumor activity in a patient who was previously treated with multiple drug modalities including anti-PD-1. The dose-escalation at 10 mg/kg and dose expansion are ongoing. Clinical trial information: ChiCTR2100052887 .
Defining risk of central nervous system relapse in acute myeloid leukemia following allogeneic stem cell transplantation.
Authors: Vincent Nicchi, Gregory Roloff, Kayeromi Gomez, Loredana Campo, Ami Badami, Stephanie Tsai, Patrick J. Stiff, Patrick Hagen
Journal: Journal of Clinical Oncology (2023)

e19009 Background: Relapse following allogeneic stem cell transplant (AlloSCT) for acute myeloid leukemia (AML) remains the commonest cause of death post-transplant. Central nervous system (CNS) relapse is a devastating complication. With an estimated incidence of 2-8%, defining those patients at high risk and the management following CNS relapse remains controversial. We sought to identify demographic, clinical, molecular, and laboratory risk factors that would predispose AML patients to CNS relapse. Methods: This was a single institution retrospective study at Loyola University Medical Center. Inclusion criteria were adult patients with AML undergoing first AlloSCT from January 2012 to June 2021. Diagnosis of CNS relapse following AlloSCT was defined as leukemic blasts detected in spinal fluid analysis in accordance with established criteria. Chi-square tests were used to test the association between the experiencing of relapse and the categorical variables recorded. Wilcoxon Rank Sum test were used to assess the relationship between relapse experience and each of the demographic variables. Due to the low count of patients with CNS relapse and in order to avoid a poor estimation of confidence limits of any effect size, we limited our analyses to descriptive statistics and univariable analyses. Results: 198 patients met inclusion criteria with 8 cases (4.0% total) identified with CNS relapse following AlloSCT. Our analysis initially characterized 44 variables including age, race, HCT-CI risk, and day 100 chimerism. Univariate analysis is shown in the table below. Of note, it revealed that 62.50% of patients with CNS relapse had a chimerism value ≤98% at day 100 post-transplant as compared to 22.58% of patients without CNS relapse (p-value 0.02). Additionally, 87.50% of the CNS relapse group versus 51.38% of the group without relapse had favorable to intermediate AML risk scores (p-value 0.07). Conclusions: We observed a 4.0% rate of CNS relapse, which is consistent with what has been repored in the literature. Our results suggest that day 100 chimerism and disease risk index may be predictive of CNS relapse. Since there is a 10.6% incidence (5/47) of eventual CNS relapse amongst those with ≤98% chimerism at day 100, these patients could be considered for a lumbar puncture and bone marrow biopsy to prevent full relapse. Further research in this topic would be valuable to provide additional AML guidance in managing this uncommon complication, such as which patients may benefit from prophylactic strategies. [Table: see text]
A phase 1 first-in-human clinical trial of HMBD-002, an IgG4 monoclonal antibody targeting VISTA, in advanced solid tumors.
Authors: Jordi Rodon Ahnert, Joshua James Gruber, Melinda L. Telli, Monica M. Mita, Alain C. Mita, Joseph W. Kim, Miguel Angel Villalona-Calero, Meera Patel, Shalini S. Yadav, Padmanee Sharma, Tom Haber, Jessica Lauren Symons, Qihui Seet, Bhushan Dharmadhikari, Dipti Thakkar, Kon Yew Kwek, Leah DiMascio, Eric Keith Rowinsky, Piers Ingram, Jerome Douglas Boyd-Kirkup
Journal: Journal of Clinical Oncology (2023)

TPS2664 Background: V-domain Ig Suppressor of T-cell Activation (VISTA), is an immune checkpoint regulator found on tumor, myeloid, and other immune cells. Its presence has been shown to enhance tumor growth, create an immunosuppressive microenvironment, and may potentially contribute to developing resistance to anti-CTLA-4 and anti-PD-1/PD-L1 therapies. Therefore, VISTA represents a promising therapeutic target. HMBD-002, a non-depleting, high-affinity IgG4 monoclonal antibody against VISTA, has demonstrated significant inhibition of tumor growth in preclinical studies, both as a monotherapy and in combination with pembrolizumab. HMBD-002 acts by increasing T-cell activity and reprogramming the suppressive tumor microenvironment to a proinflammatory antitumor phenotype. Cancer types including triple-negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC), which exhibit high expression levels of VISTA in the TME, provide a rational basis for exploring these indications in clinical studies. Methods: This phase 1/2, open-label, multi-center trial is being conducted in two parts to evaluate the safety, pharmacokinetics, and antitumor activity of HMBD-002, an IgG4 monoclonal antibody targeting VISTA, as a monotherapy and in combination with pembrolizumab. The dose-escalation stage (Part 1) will follow a standard 3 + 3 study design with weekly dosing and adaptive dose-escalation increments to determine the recommended phase 2 dose (RP2D) for subsequent disease-directed studies. Monotherapy escalation cohorts 1-4 have been completed without dose-limiting toxicities (DLTs). The dose-expansion stage (Part 2) will evaluate the antitumor activity of HMBD-002 alone and combined with pembrolizumab in patients with TNBC and NSCLC, as well as a wide range of VISTA-expressing malignancies. Exploratory analyses will be conducted to assess treatment-induced immunological changes both systemically and within the tumor microenvironment. Longitudinal blood samples will be evaluated using single-cell mass cytometry (CYTOF) and multiplex cytokine analysis. Pre and on-treatment tumor tissue samples will be assessed for VISTA &amp; PD-L1 expression using IHC. Additionally, tumor tissues will be evaluated using multiplex immunofluorescence, and gene-expression profiling. Biomarker correlations with clinical outcomes may lead to the identification of predictive markers of response to HMBD-002. Clinical trial information: NCT05082610 .
Nature and management of melanoma recurrences following adjuvant anti-PD-1 (PD1) therapy.
Authors: Rachel Woodford, Janet McKeown, Lotte Hoeijmakers, Joanna Mangana, Celeste Lebbe, Farzana Yasmin Zaman, Francisco Aya, John Marsiglio, Rachel S Goodman, Victoria Rayson, Joanna Placzke, Jolien Isabel Kessels, Egle Ramelyte, Waqas Haque, Isabella Wilson, Claudia Trojaniello, Rachel Roberts-Thomson, Caroline Robert, Georgina V. Long, Alexander M. Menzies
Journal: Journal of Clinical Oncology (2023)

9575 Background: Despite improved outcomes with the use of adjuvant PD1 therapy, approximately 50% of patients (pts) develop recurrent disease by 5 years. Data to define best management of recurrences is lacking, including whether retreatment with PD1 has benefit. Methods: This was a multicentre, international retrospective study of pts with resected stage II-IV melanoma who commenced adjuvant PD1 therapy before January 2022 and then recurred. Demographics, disease characteristics, treatment, toxicity, recurrence patterns, management and outcomes were collected. Results: 711 pts from 17 sites were included. Med age was 60 [range 16-92], 64% (N=451) were male. 641 (91%) pts were stage III (A 7%, B 24%, C 54%, D 3%), 18 (2%) stage II, 51 (7%) stage IV. 80% (N=536) underwent SLNB prior to PD1, of which 44% (N=236) went onto CLND. 635 pts (90%) received PD1, 74 (10%) PD1 + other. Med time to recurrence was 6.2 months (m) (0-68.5); 63% (N=444) recurred ON PD1, while 36% (N=257) recurred OFF. 338 pts (48%) recurred within 6m of starting adjuvant, 166 (23%) between 6-12m, 140 (20%) 12-24m and 59 (8%) after 24m. Initial recurrences were locoregional (LR) alone in 315 (44%), 307 (43%) distant alone, and 78 (11%) both. Patients with LR recurrences alone underwent definitive surgery, or surgery + radiation in 98 (31%) and 42 (13%) respectively. After initial LR management, 164 (52%) had a further local and 129 (41%) distant recurrence. Those with initial distant recurrences were managed with definitive surgery (21, 7%), surgery + radiation (8, 3%) and radiation alone (14, 5%). Further ‘second’ adjuvant therapy was given in 27% (N=86) of LR and 6% (N=25) of distant recurrences. Definitive systemic therapy at first recurrence was given in 77% (N=296) distant and 23% (N=73) LR recurrences (Table). Conclusions: Patients recurring after adjuvant PD1 therapy do so early, and often while on drug. Patients with resected recurrences often receive “second adjuvant” therapy, although whether adjuvant or definitive, outcomes are poor. Novel drug therapies and clinical trials are required for those who recur despite PD1 therapy. [Table: see text]
Evaluating genetic screening/counseling for patients diagnosed with prostate cancer who meet hereditary risk assessment based on NCCN Guidelines.
Authors: Ruben Ruiz Vega, Oluseyi Abidoye, Comfort Adewunmi, Aditya Kumar Ghosh, Andria P. Caton, Andrew Thomas Johnson
Journal: Journal of Clinical Oncology (2023)

e17117 Background: Prostate cancer is most common cancer among men and is the second leading cause of cancer deaths in American men. Genetic predisposition to cancer is increasingly noted as a cause in many cancers including prostate cancer. Genetic testing and counseling are recommended in certain groups of men; Men with or without a personal history of prostate cancer who have a family history of prostate, breast, colon, ovarian, or pancreatic cancers, especially if any of these were diagnosed under age 50 and those with metastatic prostate cancer. A recent study of 3,600 men with prostate cancer found that 17% had inherited genetic mutations that may have contributed to their cancer. Of those men, 31% of the mutations were in the BRCA genes. Because of this, familiarity and understanding of the most current clinical guidelines for genetic risk assessment are of great importance in the survivorship care of men with prostate cancer. The National Comprehensive Cancer Network (NCCN) guidelines recommends genetic assessment/counseling for genetic/familial high-risk individuals diagnosed with prostate cancer. This retrospective study reports on adherence to genetic screening based on NCCN guidelines for newly diagnosed Prostate cancer patients who were receiving treatment at Northeast Georgia Medical Center (NGMC). Methods: We obtained data using EPIC database from NGMC electronic medical records to identify patients who were diagnosed between 1/1/20-12/31/20. Data included patients who were high risk and fit the criteria for genetic testing based on NCCN as well as identifying patients who were sent for genetic testing/counsellng. The dataset was de-identified and analyzed using appropriate descriptive statistical testing. Results: A total of 42 cases for prostate cancer were reviewed. All 42 of the cases were under the age of 60 at diagnosis. A total of 13 of the cases meet the genetic/familial high-risk assessment based on NCCN guidelines. Of the 13 of the cases, only 1 case was referred for genetic counseling which was 7.6% compliance with NCCN guidelines for genetic counseling/referral. In terms of high-penetrance prostate cancer risk screening, none of the 13 cases (0%) meeting genetic/familial high-risk were screened. Based on our findings, there was poor adherence in genetic testing/counseling in high risk patients with prostate cancer at NGMC. Conclusions: This study points out poor adherence to NCCN guideline directed genetic counseling/testing in high risk patients with prostate cancer. Based on findings, it is clear that high importance should be placed on awareness on the current guidelines in relation to gene testing for patients who are high risk as this would play an important role in identifying family members who at risk and ensure early screening.